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Nuclear Lipids and Their Metabolic and Signaling Properties

  • R. Ledeen
  • G. Wu
Reference work entry

Abstract:

Nuclei have a relative paucity of lipids, perhaps accounting for the early assumption that their role in that organelle is limited to providing structural support to the nuclear envelope. In addition to the growing awareness that lipids of this double membrane structure have dynamic signaling properties, biochemists and cell biologists now recognize that lipids also occur in endonuclear compartments where they exert an astounding array of signaling capabilities with profound influence on cellular functioning. Gone also is the concept of the nucleus as passive recipient of lipids that are synthesized elsewhere in the cell and imported, since numerous enzymes have been discovered that synthesize and catabolize lipids within the nucleus. Phosphatidylinositol is synthesized in extranuclear compartments and transferred to the nucleus where it is phosphorylated to phosphatidylinositol bisphosphate, a substrate for phospholipase C. The latter generates the two second messengers, inositol trisphosphate and diacylglycerol, which draws protein kinase C to the nucleus and activates it; the polyunsaturated forms of diacylglycerol are especially active in that regard. Phosphatidylinositol bisphosophate can also react with phospholipase A2 to liberate arachidonic acid, which can in turn undergo conversion to eicosanoids within the nucleus. More saturated forms of diacylglycerol are formed by hydrolysis of phosphatidylcholine, some of which are disaturated in terms of the aliphatic chains. Phosphatidylcholine is synthesized within the nucleus, as evidenced in the presence of the Kennedy pathway enzymes. The diacylglycerol form of signaling is terminated by diacylglycerol kinase, several isoforms of which occur in the nucleus. Sphingolipids such as sphingomyelin also have a prominent role in nuclear signaling, the main metabolic product being ceramide that is generated by sphingomyelinase. Evidence has suggested that the ratio of ceramide to diacylglycerol is a form of regulatory control critical for homeostatic properties of the nucleus. Sphingomyelin comprises a significant component of chromatin lipids and its variation in relation to cholesterol and phosphatidylcholine indicated that nuclear matrix lipids are metabolized independently of chromatin lipids. Current and prior studies suggest several key processes involving RNA and DNA reactivity that are dependent on these lipid-initiated events. Considerable interest has focused on inositides whose activities include promotion of transcription through neutralizing histone-mediated repression. These and other lipids occur in specles, the microdomains that are believed to contain molecules involved in splicing of pre-mRNA. Nuclei from mammalian cells all have the same general structure consisting of the double-membrane envelope and various less well-defined endonuclear compartments. The two membranes that make up the nuclear envelope are quite different in lipid composition and function: the outer membrane is continuous with the endoplasmic reticulum and bears many similarities to the latter, whereas the inner membrane is unique and contains elements that mediate communication between nucleoplasm and the lumen of the nuclear envelope. The latter is a calcium storage site, continuous with that of the endoplasmic reticulum, from which calcium can be released in signaling mode to the nucleoplasm and to which excess calcium can be transferred via a sodium–calcium exchanger in conjunction with GM1 ganglioside. This was shown to exert an important neuroprotective function in neural cells. GM1 and GD1a are the primary species of gangliosides found in the nuclear envelope; those together with GD3 are also present in some endonuclear domains. These ganglioside characteristics of the nucleus were observed in neural cells of various types and in certain nonneural cells as well.

Keywords

Nuclear Envelope Nuclear Matrix Nuclear Pore Complex Cerebellar Granule Neuron Inositol Trisphosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:

CGN

cerebellar granule neurons

CER

ceramide

DAG

diacylglycerol

DGK

diacylglycerol kinase

ER

endoplasmic reticulum

INM

inner nuclear membrane

Ins(1,4,5)P3

inositol trisphosphate

NCX

sodium–calcium exchanger

NE

nuclear envelope

ONM

outer nuclear membrane

PGHS

postaglandin H Synthase

PI3K

PtdIns(4,5)P2 3-kinase

PI-PLC

phosphoinositide specific phospholipase C

PL

phospholipid

PLA2

phospholipase A2

PLase

phospholipase

PLC

phospholipase C

PLD

phospholipase D

PtdCho

phosphatidylcholine

PtdEtn

phosphatidylethanolamine

PtdIns

phosphatidylinositol

PtdIns(4)P

phosphatidylinositol 4-phosphate

PtdIns(4,5)P2

phosphatidylinositol 4,5-bisphosphate

PtdOH

phosphatidic acid

PtsSer

phosphatidylserine

S-1-P

sphingosine-1-phosphate

SM

sphingomyelin

SMase

sphingomyelinase. Nomenclature of individual phospholipids is in comformity with the recommendations of the IUPAC-IUB Commission on Nomenclature of Lipids. Ganglioside nomenclature is that of the JCBN recommendations [Eur. J. Biochem. 257: 293–298 (1998)]

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© Springer Science+Business Media, LLC 2009

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  • R. Ledeen
  • G. Wu

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